Combination of Interleukin-6, C-Reactive Protein and Procalcitonin Values as Predictive Index of Sepsis in Course of Fever Episode in Adult Haematological Patients: Observational and Statistical Study.

Haematological patients represent a vulnerable population to opportunistic infections, mainly due to the disease itself and chemotherapy-induced neutropenia. The level of immune suppression strongly increases the importance of timely antibiotic treatment in order to prevent sepsis-related mortality. During the initial fever episode, serum biomarkers are usually used to estimate the probability of blood stream infection prior to the results of microbial diagnosis. A new serum biomarker combination study on a febrile haematological population, including C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT), is proposed in order to improve their predictive accuracy. In our prospective study, CRP, IL-6 and PCT were evaluated in 34 immunosuppressed haematological patients immediately after the onset of 51 fever episodes, either during the course of standard chemotherapy or high-dose chemotherapy and autologous stem cell transplant. The fever episodes were divided into documented infections and fever alone. Receiver operating characteristic analysis (ROC) was performed for each biomarker and a combination of all three biomarkers (multiROC) to define a new predictive index. Significant differences were evidenced between the two groups (documented infection and no infection) for both PCT and IL-6 (p = 0.03 and p = 0.035, respectively), but none for CRP (p = 0.1). The composite parameter is more reliable than any single biomarker alone, with an area under the curve (AUC) of 79% and with high sensitivity and specificity. IL-6 gave the closest response compared to the composite index. Composite parameters of serum biomarkers could be used for an early diagnosis of infection at fever onset in haematological patients.

C-Reactive Protein Monitoring and Clinical Presentation of Fever as Predictive Factors of Prolonged Febrile Neutropenia and Blood Culture Positivity after Autologous Hematopoietic Stem Cell Transplantation-Single-Center Real-Life Experience.

BACKGROUND: Febrile neutropenia (FN) is a medical emergency that requires urgent evaluation, timely administration of empiric broad-spectrum antibiotics and careful monitoring in order to optimize the patient's outcome, especially in the setting of both allogeneic and autologous hematopoietic stem cell transplant (ASCT). METHODS: In this real-life retrospective study, a total of 49 consecutive episodes of FN were evaluated in 40 adult patients affected by either multiple myeloma (thirty-eight) or lymphoma (eleven), following ASCT, with nine patients having fever in both of the tandem transplantations. RESULTS: Febrile neutropenia occurred a median of 7 days from ASCT. Median duration of FN was 2 days, with 25% of population that had fever for at least four days. Ten patients had at least one fever spike superior to 39 °C, while the median number of daily fever spikes was two. Twenty patients had positive blood cultures with XDR germs, namely Pseudomonas aeruginosa and Klebsiella pneumoniae, present in seven cases. ROC analysis of peak C-reactive protein (CRP) values was conducted based on blood culture positivity and a value of 12 mg/dL resulted significant. Onset of prolonged fever with a duration greater than 3 days was associated with the presence of both a peak number of three or more daily fever spikes (p = 0.02) and a body temperature greater than 39 °C (p = 0.04) based on odds ratio (OR). Blood culture positivity and peak CRP values greater than 12 mg/dL were also associated with prolonged fever duration, p = 0.04, and p = 0.03, respectively. The probability of blood culture positivity was also greater in association with fever greater than 39 °C (p = 0.04). Furthermore, peak CRP values below the cut-off showed less probability of positive blood culture (p = 0.02). CONCLUSIONS: In our study, clinical characteristics of fever along with peak CRP levels were associated with a higher probability of both prolonged fever duration and positive blood culture, needing extended antibiotic therapy.

NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia.

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for "Differentially Expressed Genes" (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.